dbSNP rs4986782: NAT1:p.Arg187Gln (chr8-18222607-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000662.8(NAT1):c.560G>A(p.Arg187Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,612,688 control chromosomes in the GnomAD database, including 290 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.014 ( 29 hom., cov: 32)

Exomes 𝑓: 0.017 ( 261 hom. )

Consequence

NAT1
NM_000662.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64

Variant links:

Genes affected

NAT1 (HGNC:7645): (N-acetyltransferase 1) This gene is one of two arylamine N-acetyltransferase (NAT) genes in the human genome, and is orthologous to the mouse and rat Nat2 genes. The enzyme encoded by this gene catalyzes the transfer of an acetyl group from acetyl-CoA to various arylamine and hydrazine substrates. This enzyme helps metabolize drugs and other xenobiotics, and functions in folate catabolism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

NAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033810735).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.014 (2124/152242) while in subpopulation NFE AF= 0.0187 (1269/68012). AF 95% confidence interval is 0.0178. There are 29 homozygotes in gnomad4. There are 1115 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2124 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAT1	NM_000662.8 link	c.560G>A	p.Arg187Gln	missense_variant	Exon 3 of 3	ENST00000307719.9	NP_000653.3	P18440

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAT1	ENST00000307719.9 link	c.560G>A	p.Arg187Gln	missense_variant	Exon 3 of 3	1	NM_000662.8	ENSP00000307218.4		P18440

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2125

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.00884

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0496

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0187

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0145

AC:

3616

AN:

249910

Hom.:

AF XY:

0.0142

AC XY:

1913

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.00321

Gnomad AMR exome

AF:

0.00589

Gnomad ASJ exome

AF:

0.00312

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00358

Gnomad FIN exome

AF:

0.0441

Gnomad NFE exome

AF:

0.0194

Gnomad OTH exome

AF:

0.0130

GnomAD4 exome

AF:

0.0175

AC:

25527

AN:

1460446

Hom.:

261

Cov.:

AF XY:

0.0170

AC XY:

12324

AN XY:

726512

show subpopulations

Gnomad4 AFR exome

AF:

0.00246

Gnomad4 AMR exome

AF:

0.00697

Gnomad4 ASJ exome

AF:

0.00300

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00343

Gnomad4 FIN exome

AF:

0.0438

Gnomad4 NFE exome

AF:

0.0194

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

AF:

0.0140

AC:

2124

AN:

152242

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1115

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00318

Gnomad4 AMR

AF:

0.00883

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0496

Gnomad4 NFE

AF:

0.0187

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0175

Hom.:

Bravo

AF:

0.0107

TwinsUK

AF:

0.0205

AC:

ALSPAC

AF:

0.0166

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0169

AC:

145

ExAC

AF:

0.0141

AC:

1714

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0163

EpiControl

AF:

0.0188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

T;T;T;T;.;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.74

.;T;.;.;T;.

MetaRNN

Benign

0.0034

T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.1

L;L;L;L;.;L

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.5

N;N;N;N;N;N

REVEL

Benign

0.068

Sift

Benign

0.36

T;T;T;T;T;T

Sift4G

Benign

0.46

T;T;T;T;T;T

Polyphen

0.81

P;P;P;P;P;P

Vest4

0.043

MPC

0.039

ClinPred

0.033

GERP RS

1.2

Varity_R

0.095

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over